A clinician's guide to addressing cardiovascular health based on a revised AHA framework.

The American Heart Association recently published updates to its definition of cardiovascular health (CVH) in its Presidential Advisory called Life's Essential 8. In particular, the update from Life's Simple 7 added a new component of sleep duration and refined definitions of prior components, including measurement of diet, nicotine exposure, blood lipids, and blood glucose. Physical activity, BMI, and blood pressure were unchanged. Together, these eight components create a composite CVH score that clinicians, policy-makers, patients, communities, and businesses can utilize to communicate in a consistent way. Life's Essential 8 also emphasizes the critical role of addressing social determinants of health to improve these individual CVH components, which strongly correlate with future cardiovascular outcomes. This framework should be used across the life spectrum including during pregnancy and childhood to allow improvements in and prevention of CVH at critical time-points. Clinicians can use this framework to advocate for digital health technologies and societal policies that help address and more seamlessly measure the 8 components of CVH with the goal of increasing quality and quantity of life.

Untargeted metabolomics of perfusate and their association with hypothermic machine perfusion and allograft failure.

Although hypothermic machine perfusion (HMP) is associated with improved kidney graft viability and function, the underlying biological mechanisms are unknown. Untargeted metabolomic profiling may identify potential metabolites and pathways that can help assess allograft viability and contribute to organ preservation. Therefore, in this multicenter study, we measured all detectable metabolites in perfusate collected at the beginning and end of deceased-donor kidney perfusion and evaluated their associations with graft failure. In our cohort of 190 kidney transplants, 33 (17%) had death-censored graft failure over a median follow-up of 5.0 years (IQR 3.0-6.1 years). We identified 553 known metabolites in perfusate and characterized their experimental and biological consistency through duplicate samples and unsupervised clustering. After perfusion-time adjustment and false discovery correction, six metabolites in post-HMP perfusate were significantly associated with death-censored graft failure, including alpha-ketoglutarate, 3-carboxy-4-methyl-5-propyl-2-furanpropanoate, 1-carboxyethylphenylalanine, and three glycerol-phosphatidylcholines. All six metabolites were associated with an increased risk of graft failure (Hazard Ratio per median absolute deviation range 1.04-1.45). Four of six metabolites also demonstrated significant interaction with donation after cardiac death with notably greater risk in the donation after cardiac death group (Hazard Ratios up to 1.69). Discarded kidneys did not have significantly different levels of any death-censored graft failure-associated metabolites. On interrogation of pathway analysis, production of reactive oxygen species and increased metabolism of fatty acids were upregulated in kidneys that subsequently developed death-censored graft failure. Thus, further understanding the role of these metabolites may inform the HMP process and help improve the objective evaluation of allograft offers, thereby reducing the discard of potentially viable organs.

A Review of Donor Acute Kidney Injury and Posttransplant Outcomes.

Although over 90 000 people are on the kidney transplant waitlist in the United States, some kidneys that are viable for transplantation are discarded. Transplant surgeons are more likely to discard deceased donors with acute kidney injury (AKI) versus without AKI (30% versus 18%). AKI is defined using changes in creatinine from baseline. Transplant surgeons can use DonorNet data, including admission, peak, and terminal serum creatinine, and biopsy data when available to differentiate kidneys with AKI from those with chronic injury. Although chronic kidney disease is associated with reduced graft survival, an abundance of literature has demonstrated similar graft survival for deceased donors with AKI versus donors without AKI. Donors with AKI are more likely to undergo delayed graft function but have similar long-term outcomes as donors without AKI. The mechanism for similar graft survival is unclear. Some hypothesized mechanisms include (1) ischemic preconditioning; (2) posttransplant and host factors playing a greater role in long-term survival than donor factors; and (3) selection bias of transplanting only relatively healthy donor kidneys with AKI. Existing literature suggests transplanting more donor kidneys with stage 1 and 2 AKI, and cautious utilization of stage 3 AKI donors, may increase the pool of viable kidneys. Doing so can reduce the number of people who die on the waitlist by over 500 every year.

Urine Injury Biomarkers Are Not Associated With Kidney Transplant Failure.

BACKGROUND: Kidneys transplanted from deceased donors with serum creatinine-defined acute kidney injury (AKI) have similar allograft survival as non-AKI kidneys but are discarded at a higher rate. Urine injury biomarkers are sensitive markers of structural kidney damage and may more accurately predict graft outcomes. METHODS: In the 2010-2013 multicenter Deceased Donor Study of 2430 kidney transplant recipients from 1298 donors, we assessed the association of donor urine injury biomarkers microalbumin, neutrophil gelatinase-associated lipocalin, kidney injury molecule-1, IL-18, and liver-type fatty acid binding protein with graft failure (GF) and death-censored GF (dcGF) using Cox proportional hazard models (median follow-up 4 y). We examined if serum creatinine-defined donor AKI modified this association to assess the relationship between subclinical donor AKI (elevated biomarkers without creatinine-defined AKI) and GF. Through chart review of a subcohort (1137 recipients), we determined associations between donor injury biomarkers and a 3-year composite outcome of GF, mortality, or estimated glomerular filtration rate ≤ 20mL/min/1.73m. RESULTS: Risk of GF, dcGF, and 3-year composite outcome did not vary with donor injury biomarker concentrations after adjusting for donor, transplant, and recipient characteristics (adjusted hazard ratio ranged from 0.96 to 1.01 per log-2 increase in biomarker). Subclinical injury in transplanted kidneys without AKI was not associated with GF. CONCLUSIONS: AKI measured using injury biomarkers was not associated with posttransplant graft outcomes (at median 4 y posttransplant). When assessing posttransplant graft viability, clinicians can prioritize other donor and recipient factors over donor kidney injury, measured by either serum creatinine or urine injury biomarkers.

Cloaking as a Community: Re-imagining the White Coat Ceremony With a Medical School Learning Community.

The Johns Hopkins School of Medicine's Learning Community-White Coat Ceremony (LC-WCC) is held each spring as a learning community (LC) event. Learning communities (LCs) connect people to learn and work across boundaries to achieve a shared goal. The LC-WCC invites first-year students to collaborate with school leaders, define the class professional values, and innovate with community members. Class-elected student leaders recruit peers to join committees to plan and lead several aspects of the ceremony, including a class-nominated speaker, a personal statements presentation, a patient inclusion presentation, a class-authored statement of values, and artistic performances. Student cloaking is performed by LC advisors in their LC small groups. A 2015 post-LC-WCC survey asking students to compare experiences of a traditional Stethoscope Ceremony (SC) with the LC-WCC found that the latter significantly increased students' sense of accomplishment (38% vs 68%, P < .001), sense of connection to the school (59% vs 82%, P < .001), to classmates (71% vs 93%, P < .001), and to the event (42% vs 76%, P < .001). Cloaking as a community is an effective way for a medical school LC to instill a greater sense of community and student leadership in this milestone celebration of humanistic values in medicine.

Comparing Outcomes between Antibody Induction Therapies in Kidney Transplantation.

Kidney transplant recipients often receive antibody induction. Previous studies of induction therapy were often limited by short follow-up and/or absence of information about complications. After linking Organ Procurement and Transplantation Network data with Medicare claims, we compared outcomes between three induction therapies for kidney recipients. Using novel matching techniques developed on the basis of 15 clinical and demographic characteristics, we generated 1:1 pairs of alemtuzumab-rabbit antithymocyte globulin (rATG) (5330 pairs) and basiliximab-rATG (9378 pairs) recipients. We used paired Cox regression to analyze the primary outcomes of death and death or allograft failure. Secondary outcomes included death or sepsis, death or lymphoma, death or melanoma, and healthcare resource utilization within 1 year. Compared with rATG recipients, alemtuzumab recipients had higher risk of death (hazard ratio [HR], 1.14; 95% confidence interval [95% CI], 1.03 to 1.26; P<0.01) and death or allograft failure (HR, 1.18; 95% CI, 1.09 to 1.28; P<0.001). Results for death as well as death or allograft failure were generally consistent among elderly and nonelderly subgroups and among pairs receiving oral prednisone. Compared with rATG recipients, basiliximab recipients had higher risk of death (HR, 1.08; 95% CI, 1.01 to 1.16; P=0.03) and death or lymphoma (HR, 1.12; 95% CI, 1.01 to 1.23; P=0.03), although these differences were not confirmed in subgroup analyses. One-year resource utilization was slightly lower among alemtuzumab recipients than among rATG recipients, but did not differ between basiliximab and rATG recipients. This observational evidence indicates that, compared with alemtuzumab and basiliximab, rATG associates with lower risk of adverse outcomes, including mortality.

Sleep problems and suicide attempts among adolescents: a case-control study.

This study used a case-control design to compare sleep disturbances in 40 adolescents who attempted suicide with 40 never-suicidal adolescents. Using hierarchical logistic regression analyses, we found that self-reported nighttime awakenings were significantly associated with attempted suicide, after controlling for antidepressant use, antipsychotic use, affective problems, and being bullied. In a separate regression analysis, the parent-reported total sleep problems score also predicted suicide attempt status, controlling for key covariates. No associations were found between suicide attempts and other distinct sleep problems, including falling asleep at bedtime, sleeping a lot during the day, trouble waking up in the morning, sleep duration, and parent-reported nightmares. Clinicians should be aware of sleep problems as potential risk factors for suicide attempts for adolescents.

Coverage for low-income immigrant children increased 24.5 percent in states that expanded CHIPRA eligibility.

The Children's Health Insurance Program Reauthorization Act (CHIPRA) of 2009 provided states with the option of expanding eligibility for federally funded public insurance to low-income immigrant children within their first five years of legal residence in the United States. By 2011 twenty states and the District of Columbia had adopted that option. Using cross-sectional data from the 2003, 2007, and 2011-12 National Survey of Children's Health, we compared trends in coverage and access to care among immigrant children in states that did expand eligibility to children in states that did not. Compared to immigrant children in states that did not expand eligibility, children in states expanding eligibility experienced a 24.5 percent increase in insurance coverage, largely due to greater enrollment in public insurance. Immigrant children in states that expanded eligibility also experienced significant reductions in unmet health care needs, compared to their counterparts in nonexpansion states. Disparities relative to children in nonimmigrant families were substantially reduced in states that expanded eligibility, compared to states that did not. Expanding eligibility for federally funded public insurance to immigrant children within their first five years of legal residence in other states could improve coverage for immigrant children and might also increase access to care.